Bruce N. Cronstein, Joseph R. Bertino
Birkhäuser, Dec 6, 2012 - Medical - 139 pages
Although surprising, it seems fitting that a drug developed at the dawn of the era of rational drug design and therapeutics, methotrexate, should remain in common use for the therapy of so many different kinds of illnesses. Moreover, methotrexate has completely revolutionized the way in which medicine is practiced in a number of speciality areas. First developed to treat malignancies, methotrexate is now commonly used to treat gynecological problems, inflammatory arthritis, skin disease and probably other ailments as well. This work is designed to give a broad overview of the history of methotrexate's development, its prior use and its current therapeutic uses. As discussed in Chapter I, aminopterin and methotrexate were designed to inhibit mammalian folate metabolism but the concept of folic acid antag onism was soon applied to the development of antibacterial and anti parasitic agents. Trimethoprim and sulfa drugs were among the first antibiotics developed and they also remain quite useful today for the treat ment of a variety of infections.
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activity acute lymphoblastic leukemia adenosine agents Alarcón GS aminopterin antifolate Arth Rheum Arthritis Rheum associated Bertino JR biochemical Biol Chem blasts Cancer Res cell lines cellular chemotherapy cisplatin Clin Oncol clinical corticosteroids cytokines decreased dermatomyositis DHFR dihydrofolate reductase disease dose of methotrexate drug ectopic pregnancy effects of methotrexate efficacy enzyme folate folic acid FPGS gamma-glutamyl hydrolase gene high dose high-dose methotrexate human increased inflammatory inhibitor inhibits intrathecal Kamen BA leucovorin leukemia cells levels liver biopsy low dose methotrexate low-dose lymphocytic lymphoma malignant mercaptopurine metabolism metho methotrexate in rheumatoid methotrexate treatment MTX polyglutamates MTX resistance neutrophils nodulosis osteosarcoma Pancytopenia patients treated patients with rheumatoid pediatric Pharmacol protein psoriasis receptors reduced folate carrier regimen reported resistance to MTX Rheum Rheum 38 rheumatoid arthritis patients rheumatoid factor Rheumatol 22 sarcoma serum studies synthesis therapeutic therapy for rheumatoid tissue toxicity transport treated with methotrexate treatment of rheumatoid tubal tumors vitro